Major Research Areas

Researchers in the College of Graduate Studies focus their efforts where it truly matters—on the diseases and illnesses that affect many people. Much of our research activity is grouped into four areas of concentration: cancer; infectious diseases; disorders of the nervous system; and diabetes, metabolic disorders and cardiovascular diseases.

Research Interests

Publications

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Research

Integrin Regulation of the Leukocyte Inflammatory Phenotype

Integrins are the cellular receptors for the proteins which constitute the extracellular matrix of all tissues. The binding of integrin receptors to extraceullular proteins permits cell adhesion and migration during development, wound healing, and inflammation. White blood cells, or leukocytes, are extremely dependent upon integrin receptor recognition of matrix proteins in order to exit the vasculature and resolve inflammatory events within the tissues. Recently it has been recognized that integrin receptors not only provide a physical link between cells and substrates, but also transduce signals to the cell which affect cell behavior.

Our laboratory studies two aspects of leukocyte integrin biology. First, how does the leukocyte utilize these receptors to mediate selective adhesion and migration through complex extracellular tissues? Second, how does the ligation of integrin receptors affect leukocyte behavior? Defining integrin biology at a molecular level, including delineation of required signalling molecules, will produce additional targets for pharmacologic intervention in diseases as diverse as cancers and inflammation.

A recent new direction of the lab is determining control of the actin cytoskeleton. We are testing a new hypothesis that nucleation of cytoskeletal actin originates with the adhesion site - somewhat at odds with currently accepted models. This project has really pushed us into some high tech microscopy approaches that mesh nicely with our cellular, biochemical, and molecular approaches. A new NIH grant, beginning 7/1/04 should push this work along nicely.

The laboratory utilizes techniques ranging from molecular biology to whole animal inflammation models, with an emphasis on cell biology and protein biochemistry. Additional areas of interest include cortical cytoskeleton, signalling paths, cell-cell junctions, infectious pathogens, polarity, metastasis, development, hemostasis and thombosis. While leukocyte behavior remains a major laboratory focus, we also study a variety of vascular and tissue cells, both primary and immortal lines.

Boettiger, D., Huber, F., Lynch, L., and Blystone, S.D. Activation of avb3 -vitronectin binding is a multistage process in which increases in bond strength are dependent on Y747 and Y759 in the Cytoplasmic Domain of b3, Molecular Biology of the Cell , 12:5, p.1227-1237, 2001.